5 pág.


DisciplinaFarmacognosia I619 materiais4.486 seguidores
Pré-visualização4 páginas
which contains more than 200
patients and done cooperatively at different institutions to
evaluate the ef\ufb01cacy of escin to improve sperm quality in male
patients with varicocele-associated infertility.
Among the four possible mechanisms by which varicocele
results in male infertility stated in the Introduction part, venous
stasis and testicular oxidative stress have been paid much
attention in recent clinical studies (Cavallini et al. 2003; Oliva et
al. 2008; Turner and Lysiak 2008). Escin has the function of anti-
oxidative stress which directly targets at one of the proposed
mechanisms mentioned above (Jarow 2001; Kamischke and
Nieschlag 2001; Marmar 2001; Naughton et al. 2001; Sirtori
2001; Carrasco and Vidrio 2007; Oliva et al. 2008). In fact, the
primary pathological changes of spermatic varicocele include
venous tortuosity, thinner venous wall, dysplasia of venous wall
muscles, \ufb01brosis of vessel wall and atrophy of outer membrane
and middle layer. These chronic in\ufb02ammation and changes in
hemodynamic \ufb01nally cause this disorder (Jarow 2001; Kamischke
and Nieschlag 2001; Marmar 2001; Naughton et al. 2001). Escin
can inhibit lysosome in serum and reduces the permeability of
capillary vessel (Sirtori 2001; Carrasco and Vidrio 2007). It can
also protect collagen \ufb01ber of venous wall and increase wall
tension and strength, which will help the recovery of tension and
contraction function damaged by lesions on venous wall.
Furthermore, it can increase venous drainage which will reduce
venous congestion (Sirtori 2001; Carrasco and Vidrio 2007). Thus,
escin presents two pharmacodynamic actions: anti-edematous
properties and venotonic properties. In fact, it also has anti-
in\ufb02ammatory activities (Carrasco and Vidrio 2007; Sirtori 2001).
In this study, escin helped reduce the diameter of 47.0% of the
spermatic veins (Table 3), which might be one of the anatomical
and physiological bases for escin to improve sperm quality.
Therefore, escin targets not only in the testis oxidative stress,
but also in the venous stasis and chronic in\ufb02ammation of the vein,
which are the three important proposed pathogenic mechanisms
ery group (n ¼ 48) Escin group (n ¼ 106)
Percentage (%) No. Percentage (%)
33.3 34 32.1
35.4 27 25.5
68.8\ufffd 61 57.5\ufffd
31.3 45 42.5
Y. Fang et al. / Phytomedicine 17 (2010) 192\u2013196 195
Table 2
The improvement of sperm motility (Grade a+Grade b) after escin treatment.
Control group (n ¼ 65)
No. Percentage (%)
Highly effective 10 15.4
Effective 20 30.8
Overall effective 30 46.2
Not effective 35 53.8
Note: Compared to the control group.
\ufffd Po0.05.
Table 3
The improvement of the diameter of spermatic vein of 151 sides in 106 cases after
Mild (n ¼ 96) Moderate (n ¼ 45)
No. Percentage (%) No. Perce
Highly effective 11 11.5 13 28.9
Effective 29 30.2 16 35.6
Overall effective 40 41.7 29 64.4
Not effective 56 58.3 16 35.6
causing varicocele-associated infertility. Thus, it is not surprising
that escin can improve sperm quality in male patients with
varicocele-associated infertility.
It is worthwhile to point out that this study showed that the
escin treatment was not effective for patients with severe
varicocele (the diam of the spermatic vein44mm). This suggests
that there is some degree of correlation between the severity of
varicocele and the ef\ufb01cay of escin. One explanation might be due
to the fact that the venous walls in patients with severe varicocele
have been destroyed severely so that they lost their ability to
recover their tension and function.
In fact, this study demonstrates that escin is not only very
effective to improve sperm quality but also it is well tolerated.
Only very low frequencies of mild adverse effects were observed
during treatment, most of which resolved without further
symptomatic drug therapy after advising the patients to take
escin after meal. Escin has little effect on vital signs, blood counts,
liver or kidney function. Therefore, escin is a safe drug to improve
sperm quality in male patients with varicocele-associated in-
In this study, all groups including the control group are given
composite medicines due to ethic consideration. Thus, it is
dif\ufb01cult to pinpoint that the improvement in sperm quality is
Note: Compared to the severe subgroup.
\ufffd Po0.05. Compared to the mild subgroup.
\ufffd\ufffd Po0.05.
Table 4
Adverse effects observed during treatment.
Control group (n ¼ 65) Sur
No. Percentage (%) No.
Fatigue 3 4.6 3
Stomach irritation 2 3.1 2
Anorexia 1 1.5 1
Nausea 3 4.6 1
Vomiting 0 0.0 1
Diarrhea 0 0.0 0
Constipation 0 0.0 0
Skin rash 0 0.0 0
Other 0 0.0 0
in treatment.
Severe (n ¼ 10) Total (n ¼ 151)
ge (%) No. Percentage (%) No. Percentage (%)
0 0.0 24 15.9
2 20.0 47 31.1
2 20.0 71 47.0
8 80.0 80 53.0
Percentage (%) No. Percentage (%)
43.8 30 28.3
33.3 29 27.4
77.1\ufffd 59 55.7
22.9 47 44.3
ery group (n ¼ 48) Escin group (n ¼ 106)
due to escin alone or it is because escin has synergistic effect with
the composite medicines. Obviously, in the future, it is necessary
to design a study in animal models for spermatic varicocele which
includes a pure placebo group and an escin group.
In conclusion, escin is a safe and effective drug to improve
semen quality in male patients with varicocele-associated in-
fertility probably by reducing testis oxidative stress, decreasing
in\ufb02ammatory responses, promoting the recovery of tension and
contraction function damaged by lesions on venous walls. It
provides new alternative treatment for male varicocele-associated
infertility, especially for patients with mild or moderate varicocele.
Con\ufb02ict of interest
The authors have no con\ufb02ict of interest.
Disclosure statement: The authors have nothing to disclose.
We thank Dr. Vincent DeMarco and Mr. Edward Downey from
the University of Missouri for their helpful discussion.
gery group (n ¼ 48) Escin group (n ¼ 106)
Percentage (%) No. Percentage (%)
6.3 5 4.7
4.2 6 5.7
2.1 3 2.8
2.1 4 3.8
2.1 2 1.9
0.0 0 0.0
0.0 0 0.0
0.0 0 0.0
0.0 0 0.0
Bielanski, T.E., Piotrowski, Z.H., 1999. Horse-chestnut seed extract for chronic
venous insuf\ufb01ciency. J. Fam. Pract. 48, 171\u2013172.
Carrasco, O.F., Vidrio, H., 2007. Endothelium protectant and contractile effects of
the antivaricose principle escin in rat aorta. Vascul. Pharmacol. 47, 68\u201373.
Cavallini, G., Biagiotti, G., Ferraretti, A.P., Gianaroli, L., Vitali, G., 2003. Medical therapy
of oligoasthenospermia associated with left varicocele. B. J. U. Int. 91, 513\u2013518.
Cavallini, G., Ferraretti, A.P., Gianaroli, L., Biagiotti, G., Vitali, G., 2004. Cinnoxicam
and L-carnitine/acetyl-L-carnitine treatment for idiopathic and varicocele-
associated oligoasthenospermia. J. Androl. 25, 761\u2013770.
Devin, R., Branchereau, A., Bourgoin, M.C., 1976. Traitement pr\ufffdeventif et curatif des
oed\ufffdemes en pathologie chirurgicale par le R\ufffdeparil intraveineux. Mediterr. Med.
94, 105\u2013109.
Frick, R.W., 2000. Three treatments for chronic venous insuf\ufb01ciency: escin,
hydroxyethylrutoside, and da\ufb02on. Angiologica 51, 197\u2013205.
Gualtieri, L., 1978. L\u2019azione della escina nell\u2019edema post-operatorio. Gazz. Med. Ital.
137, 339\u2013344.
Hefti, F., Kappeler, U., 1975. Klinischer Untersuchung von Aescin-Ampullen bei
postoperativen und posttraumatischen Oedemen. Schweiz. Rundsch. Med.
Praxis 64, 73\u201377.
Jarow, J.P., 2001. Effect of varicocele on male fertility. Hum. Reprod. Update 7, 59\u201364.
Kamischke, A., Nieschlag, E., 2001. Varicocele treatment in the light of evidence-
based andrology. Hum. Reprod. Update 7, 65\u201369.
Kim, H.H., Goldstein, M., 2008. Adult varicocele. Curr. Opin. Urol. 18, 608\u2013612.
Marmar, J.L., 2001. Varicocele and male infertility. Part II. The pathophysilogy of
varicocele in the light of current molecular and genetic information. Hum.
Reprod. Update 7, 461\u2013472.
Mouly, R., 1974. Tratement pr\ufffdeventif et curatif de l\u2019oed\ufffdeme post-op\ufffderatoire en
chirurgie plastique par le 1323 AN. Gaz. Med. Fr. 81, 3127\u20133133.